Soluble Urokinase-type Plasminogen Activator Receptor Predicts All-cause 5-Year Mortality in Ischemic Stroke and TIA

Onatsu, Juha; Taina, Mikko; Mustonen, Pirjo; Hedman, Marja; Muuronen, Antti; Arponen, Otso; Korhonen, Miika; Jäkälä, Pekka; Vanninen, Ritva; Pulkki, Kari

doi:10.21873/invivo.11070

Cited by 9 publications

(8 citation statements)

References 41 publications

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“…In the present study, it was observed that suPAR concentration fails to differentiate between stroke due to LAO (in all cases caused by symptomatic atherosclerosis) or to other causes. This is partially in line with the findings of Onatsu et al [ 29 ]. The authors reported that although elevated suPAR allows prediction of all-cause mortality due to stroke, it does not differentiate between all stroke types.…”

Section: Discussionsupporting

confidence: 93%

“…To the best of our knowledge, while many papers investigated prognostic factors of stroke outcome [ 35 ], this is the first study to investigate correlations between suPAR levels in ischemic stroke and the functional outcome of patients with a 3-year long follow-up. suPAR was proposed as a predictor of 5-year all-cause mortality in a study by Onatsu et al [ 29 ] In the present study, such a correlation was not observed. This may be due to a shorter follow-up (3 vs. 5 years) and a smaller patient group (51 vs. 117).…”

Section: Discussioncontrasting

confidence: 73%

“…Few studies focused on the evaluation of suPAR levels in plasma in association with the histopathological assessment of atherosclerotic plaque morphology [ 26 ]. A study by Onatsu et al showed that suPAR concentration was higher in patients after a stroke/TIA due to large-artery atherosclerosis compared to small-vessel disease (SVD), and that elevated plasma suPAR concentrations predicted all-cause mortality during the 5-year follow-up [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Soluble Urokinase Plasminogen Activator Receptor Levels Correlation with Other Inflammatory Factors in Prognosis of Disability and Death in Patients with Ischemic Stroke

et al. 2021

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Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker elevated in cardiovascular diseases. The aim of this 3-year follow-up prospective study was to evaluate suPAR levels in patients with a first ischemic stroke in correlation with CRP, PCT, NT-proCNP and endothelin 1-21 and to investigate the impact of suPAR on the outcome. Fifty-one patients (mean age 73.7+ = 11.9 years, 26 female and 25 male) were included. Samples were collected on the first (suPAR 1), third (suPAR 3) and seventh days after stroke onset (suPAR 7). Plasma samples were analyzed using ELISA. A phone interview was conducted to collect follow-up information after 24 and 36 months (modified Rankin Scale, mRS). A positive correlation between suPAR levels and other inflammatory biomarkers (except endothelin 3) was observed. A positive correlation between suPAR 3 and mRS score at 24 months was observed (p = 0.042). The logistic regression model revealed no significant effect of suPAR on death occurrence in the first 24 months: suPAR 1 (p = 0.8794), suPAR 3 (p = 0.2757), and suPAR 7 (p = 0.3652). The suPAR level is a potential inflammatory marker in ischemic stroke, and there is a correlation with other markers. There is no major impact on mortality. However, the suPAR level is associated with a degree of disability or dependence in daily activities 2 years after a stroke.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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Soluble Urokinase Plasminogen Activator Receptor Levels Correlation with Other Inflammatory Factors in Prognosis of Disability and Death in Patients with Ischemic Stroke

et al. 2021

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“…This study sample consisted of the same patients from the prospective single-center observational EmbodeteCT Eastern Finland Study (28,35). Acute AIS/TIA patients admitted to Kuopio University Hospital between March 2005 and November 2009 because of suspected cardioembolic etiology, but without known atrial fibrillation (AF), were candidates to the study (28)(29)(30). A total of 162 patients were recruited and had AIS or TIA of cryptogenic or suspected cardiogenic etiology without AF during the enrollment.…”

Section: Methodsmentioning

confidence: 99%

Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events

Onatsu

Vanninen

Jäkälä

et al. 2020

In Vivo

Self Cite

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Background/Aim: We aimed to analyze the diagnostic value of total tau (T-tau), S-100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) as blood-based biomarkers in acute ischemic stroke (AIS) or transient ischemic attack (TIA), and their correlation with symptom severity, infarct size, etiology and outcome. Patients and Methods: A total of 102 patients with stroke and 35 with TIA were analyzed. Subacute (63.8±50.1 h) plasma T-tau was measured with the single-molecule array (Simoa) method and NSE and S100B were evaluated for comparison. We evaluated biomarkers associations with: (i) diagnosis of AIS or TIA, (ii) cerebral infarction volume in the brain computed tomography, (iii) stroke etiology, (iv) clinical stroke severity and (iv) functional outcome after three months. Results: T-tau was higher in patients with stroke [1.0 pg/ml (IQR=0.3-2.2)] than with TIA [0.5 pg/ml (IQR=0.2-1.0), p=0.02]. The levels of S100B were also increased in stroke [0.082 μg/l (IQR=0.049-0.157)] patients compared to TIA patients [0.045 μg/l (IQR=0.03-0.073), p<0.001]. However, when the results were adjusted for confounders, significance was lost. Serum levels of NSE among patients with AIS [11.85 μg/l (IQR=9.30-16.14)] compared to those with TIA [10.96 μg/l (IQR=7.98-15.33), p=0.30] were equal. T-tau and S100B concentrations significantly correlated with cerebral infarction volume (r=0.412, p<0.001) and (r=0.597, p<0.001), also after corrections (p<0.001). mRS scores at three-month follow-up correlated with T-tau (r=0.248, p=0.016) and S100B concentrations (r=0.205, p=0.045). Conclusion: For the diagnosis of TIA vs. AIS, blood T-tau and S100B concentrations discriminated only modestly. Additionally, groups were not separable after measuring of T-tau and S100B levels in the blood. T-tau and S100B concentrations correlated with the infarct size, but were not alone predictive for functional outcome at 3 months. T-tau protein is a microtubule-associated protein (MAP), expressed in the brain especially in the unmyelinated cortical axons (1). It is mostly found in neurons and to a lesser extent in astrocytes and oligodendrocytes. In nerve cells it has a critical role in the structural stabilization and formation of the neuronal cytoskeleton (2-4). Increased levels of tau protein have been detected in the cerebrospinal fluid (CSF) of patients with neurodegenerative diseases, e.g. Alzheimer's (5) and Creutzfeldt-Jakob disease (6), as well as in the CSF of those with severe head injuries (7). After neuro-axonal injury, such as acute ischemic stroke (AIS) or transient ischemic attack (TIA), tau proteins are also released to the extracellular space and can be detected both in CSF and 2577 This article is freely accessible online.

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“…Other than being instrumental in plasminogen activation, the uPA-uPAR binding also promotes the degradation of the extracellular matrix, a major event that underlies tumour progression and metastasis (Mahmood et al 2018). Recent studies proving soluble uPAR as an important independent predictor for cardiovascular events in patients with first AMI and all-cause mortality at five-year after ischaemic strokes, indicating the importance of this particular receptor and the overall uPA activity in ischaemic vascular events (Onatsu et al 2017;Wlazel et al 2019).…”

Section: Urokinase-plasminogen Activatormentioning

confidence: 99%

Urokinase Plasminogen Activator: A Potential Thrombolytic Agent for Ischaemic Stroke

Kadir

Bayraktutan

2019

Cell Mol Neurobiol

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Stroke continues to be one of the leading causes of mortality and morbidity worldwide.Restoration of cerebral blood flow by recombinant plasminogen activator (rtPA) with or without mechanical thrombectomy is considered the most effective therapy for rescuing brain tissue from ischaemic damage, but this requires advanced facilities and highly skilled professionals, entailing high costs, thus in resource-limited contexts urokinase plasminogen activator (uPA) is commonly used as an alternative. This literature review summarises the existing studies relating to the potential clinical application of uPA in ischaemic stroke patients.In translational studies of ischaemic stroke, uPA has been shown to promote nerve regeneration and reduce infarct volume and neurological deficits. Clinical trials employing uPA as a thrombolytic agent have replicated these favourable outcomes and reported consistent increases in recanalisation, functional improvement, and cerebral haemorrhage rates, similar to those observed with rtPA. Single-chain zymogen pro-urokinase (pro-uPA) and rtPA appear to be complementary and synergistic in their action, suggesting that their co-administration may improve the efficacy of thrombolysis without affecting the overall risk of haemorrhage. Large clinical trials examining the efficacy of uPA or the combination of pro-uPA and rtPA are desperately required to unravel whether either therapeutic approach may be a safe first-line treatment option for patients with ischaemic stroke. In light of the existing limited data, thrombolysis with uPA appears to be a potential alternative to rtPA-mediated reperfusive treatment due to its beneficial effects on the promotion of revascularisation and nerve regeneration.

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Soluble Urokinase-type Plasminogen Activator Receptor Predicts All-cause 5-Year Mortality in Ischemic Stroke and TIA

Cited by 9 publications

References 41 publications

Soluble Urokinase Plasminogen Activator Receptor Levels Correlation with Other Inflammatory Factors in Prognosis of Disability and Death in Patients with Ischemic Stroke

Soluble Urokinase Plasminogen Activator Receptor Levels Correlation with Other Inflammatory Factors in Prognosis of Disability and Death in Patients with Ischemic Stroke

Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events

Urokinase Plasminogen Activator: A Potential Thrombolytic Agent for Ischaemic Stroke

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